Hepatitis B virus infection specially increases risk of liver metastasis in breast cancer patients: a propensity-matched analysis
TRANSLATIONAL CANCER RESEARCH
Authors: Yu, Ping; Liu, Peng; Li, Na; Xie, Xinhua; Tang, Hailin; Wu, Jiali; Kong, Yanan; Xie, Xiaoming; Ye, Feng
Abstract
Background: Breast cancer and hepatitis B virus (HBV) infection are serious public health issues in China. But the effect of HBV infection on breast cancer remains unclear. The objective was to assess whether HBV infection was associated with prognosis of breast cancer. Methods: A retrospective database of 1,924 invasive breast cancer patients from Sun Yat-sen University Cancer Center from 2008 to 2010 was established. Propensity score matching method was applied to balance baseline parameters. Logistic regression was used for identifying the independent risk factors of liver metastasis. Prognostic outcomes were evaluated via Kaplan-Meier analysis and Cox model. Results: Primary evaluation of gross data suggested HBV infection was associated with much higher rate of liver metastasis. 642 patients were matched for analysis. The median follow-up time was about 69 months. Patients with HBV surface antigen (HBsAg) (+) had a specially higher risk of liver metastasis aside of other distant organs than those with HBsAg (-). HBsAg (-/+) was identified to be an independent risk factor of liver metastasis [odds ratio (OR), 2.651; 95% confidence intervals (CI), 1.213- 5.796; P=0.015]. HBsAg (+) was associated with liver metastasis significantly in stage III or in estrogen receptor (ER) (+) and/or progesterone receptor (PR) (+), human epidermal growth factor receptor-2 (HER-2) (-) subtype. Meanwhile, patients with HBsAg (+) had significant shorter liver metastasis-free survival (LMFS) compared with HBsAg (-) patients (P=0.041). But the difference of overall survival (OS) between the HBsAg (-) and HBsAg (+) groups reached statistically no significance (P=0.425).The multivariate analysis suggested HBsAg (+) could worsen the outcome of LMFS [hazards ratio (HR), 2.450; 95% CI, 1.169-5.135; P=0.018]. Conclusions: In breast cancer, HBsAg (+) was associated with specially a higher rate of liver metastasis and thus worsened the LMFS. HBsAg (-/+) was an independent risk factor of liver metastasis.
Large-scale genome-wide association study identifiesHLAclass II variants associated with chronic HBV infection: a study from Taiwan Biobank
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Authors: Huang, Yu-Han; Liao, Shu-Fen; Khor, Seik-Soon; Lin, Yu-Ju; Chen, Hsuan-Yu; Chang, Ya-Hsuan; Huang, Yi-Hsiang; Lu, Sheng-Nan; Lee, Hye-Won; Ko, Wen-Ya; Huang, Claire; Liu, Po-Chun; Chen, Yen-Ju; Wu, Ping-Feng; Chu, Hou-Wei; Wu, Pei-Ei; Tokunaga, Katsushi; Shen, Chen-Yang; Lee, Mei-Hsuan
Abstract
Background Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations. Aims To explore genetic variants associated with chronic HBV infection. Methods The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as chronic HBV infection. All participants were examined for whole-genome genotyping by Axiom-Taiwan Biobank Array. The human leucocyte antigen (HLA)imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of differentHLAallele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed forHLAalleles using NetMHCIIpan method. Results Located within a cluster of 450 single nucleotide polymorphisms inHLAclass II, rs7770370 (P = 2.73 x 10(-35)) was significantly associated with HBV chronicity (P-corrected < 8.6 x 10(-8)). Imputation analyses showed thatHLA-DPA1*02:02andHLA-DPB1*05:01were associated with chronic HBV, with adjusted ORs of 1.43 (1.09-1.89) and 1.61 (1.29-2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05).HLA-DRB1*13:02,HLA-DQA1* 01:02andHLA-DQB1*06:09associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17-0.58), 0.70 (0.56-0.87) and 0.33 (0.18-0.63). TheseHLAalleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein. Conclusions HLAclass II variants are relevant for chronicity after HBV acquisition.